Generic manufacturers call for changes to list of major deficiencies

Regulatory NewsRegulatory News | 20 October 2022 |  By 

Generic drug manufacturers are urging the US Food and Drug Administration (FDA) to revise its guidance on amendments to Abbreviated New Drug Applications (ANDA) under the Generic Drug Use Fee Amendments (GDUFA) to classify fewer deficiencies as “major” and avoid extended review cycles.
FDA established a docket to solicit public comments on Appendix A of the July 2018 guidance for industry on “ANDA Submissions – Amendments to Abbreviated New Drug Applications Under GDUFA.” The effort to solicit public comment was part of the GDUFA III Commitment Letter. The ANDA Amendments Guidance defines amendment classifications and categories and how they may impact an amendment’s performance goal date. Appendix A is focused on “major” deficiencies and provides a non-exhaustive list of examples. (RELATED: FDA Finalizes Guidance on GDUFA II, Regulatory Focus 3 July 2018)
Commenters asked the agency to update Appendix A to make it consistent with the tools and principles of the GDUFA III program, including utilizing alternative methods, such as Information Requests (IRs), Discipline Review Letters (DRLs) and Imminent Action, rather than relying on Complete Response Letters (CRLs), which creates significant delays, they wrote.
“Unfortunately, our experience is that review times for generics can be long, communication with FDA is often transactional rather than interactive and collaborative, and issues are often raised late in the review cycle—all elements of the generic drug review program that undermine our shared goal,” wrote Aaron Josephson, Director of Regulatory Policy and Intelligence at Teva Pharmaceuticals. “In considering changes to Appendix A, we support FDA tailoring the list of major deficiencies in favor of using alternative methods—IRs, minor deficiencies, and Imminent Action among the options—to satisfy a regulatory requirement.”
The GDUFA III Commitment Letter also defines “small” deficiencies as being issues that can be assessed by FDA within 60 days and can be addressed by clarification of scientific information, limited submission of additional data or submission of administrative information. “We propose that many of the items currently listed in Appendix A are, by this definition, small issues and therefore the generic applications to which they apply could benefit from Imminent Action,” Josephson wrote. “The use of Imminent Action will give FDA the time needed to evaluate a response from an applicant without extending the review clock and delaying generic launch by, in some cases, more than a year.”
The Association for Accessible Medicines (AAM) also called on FDA to use mechanisms other than CRLs to address deficiencies, specifically those related to absence of information.
“Many examples in Appendix A state that the lack of information in the original submission would result in a major CRL. As a result of the GDUFA III commitments, however, FDA needs to note in the guidance that the absence of information in the original ANDA may be addressed through other mechanisms (e.g., IRs, minor amendments, imminent action, Discipline Review Letters (DRL),” wrote David R. Gaugh, RPh, Executive Vice President for Sciences and Regulatory Affairs.
AAM also urged FDA to avoid the use of subjective terms like “inadequate” and “insufficient,” which currently appear in Appendix A. “This may lead to submissions unnecessarily being classified as major and contribute to inconsistent classifications and misunderstandings between FDA and applicants,” Gaugh wrote.  
Viatris, a manufacturer of generic drugs, recommended that FDA clarify that the agency can exercise flexibility in determining amendment classifications when “sufficient justification is submitted to show an amendment is minor in nature.” The company provided several examples from Appendix A that they said were incorrectly classified as major. For example, it is considered a major deficiency when a proprietary name request is denied, and a new name is submitted for consideration. This example should not be classified as a major deficiency because a similar change in a New Drug Application (NDA) has a review goal of 90 days under PDFUFA VII. The same timeline should apply to ANDAs, wrote Wayne Talton, Head of Regulatory North America for Viatris.
The International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) urged FDA not to include “excipients above inactive ingredient limit” as a major deficiency in Appendix A. This inclusion is “not justified because the [inactive ingredient database] is not complete and contains inaccuracies,” the group wrote. They called on the agency to accept bridging justifications to support excipient safety for the intended use. “To avoid deficiencies related to excipient levels used in formulations, IPEC-Americas recommends that FDA develop guidance related to bridging justification expectations,” wrote Nigel Langley, PhD, Chair of IPEC-Americas.
Public comments on Appendix A


© 2023 Regulatory Affairs Professionals Society.

Discover more of what matters to you